Methods for improved prosthetic heart valve with leaflet shelving

ABSTRACT

Described embodiments are directed toward prosthetic valve leaflets of particular configurations that control bending character. In embodiments provided herein, valve leaflets are operable to bend along a base of the valve leaflets.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/720,441, filed Sep. 29, 2017, which is a continuation of U.S. patentapplication Ser. No. 14/792,380, filed Jul. 6, 2015, now U.S. Pat. No.9,827,089, issued Nov. 28, 2017, which is a divisional of U.S. patentapplication Ser. No. 13/869,878, filed Apr. 24, 2013, now U.S. Pat. No.9,101,469, issued Aug. 11, 2015, which claims priority to ProvisionalApplication 61/739,721, filed Dec. 19, 2012, all of which areincorporated herein by reference in their entireties for all purposes.

FIELD

The present disclosure relates generally to prosthetic valves and morespecifically to synthetic flexible leaflet-type prosthetic valvedevices, systems, and methods with controlled leaflet opening.

BACKGROUND

The durability of synthetic valve leaflets is partially a function ofthe character of bending by the leaflet during the opening-closingcycle. Small radius bends, creases and intersecting creases, can producehigh stress zones in the leaflet. These high stress zones can cause theformation of holes and tears under repetitive loading.

Prosthetic valves may be delivered using surgical or transcathetertechniques. A surgical valve is implanted into a patient usingopen-heart surgical techniques. The surgical valve is usuallymanufactured to have a fixed diameter as opposed to a transcathetervalve which is required to attain a range of diameters for access anddelivery. The surgical valve is usually provided with a sewing cuffabout a perimeter of the valve to allow for suturing to the nativetissue orifice. Sewing cuffs are well known in the art.

In addition to the valve durability issues discussed above, thetranscatheter valve must also be able to withstand the handling anddeployment stresses associated with being compressed and expanded

The shape most often described as preferable is modeled after the nativehuman aortic valve. Though nature dictates the optimum shape for thenative tissues to form a heart valve, we have discovered this is nottrue for synthetic materials; accordingly, the design specified in thecurrent disclosure is instead intended to place the synthetic materialunder a minimized stress condition as compared to those based on copiesof the native valve. This is partially accomplished through reducedbuckling in the leaflet material.

There exists a need for a durable synthetic prosthetic valve that may bedelivered either surgically or endovascularly.

SUMMARY

Described embodiments are directed to an apparatus, system, and methodsfor valve replacement, such as cardiac valve replacement. Morespecifically, described embodiments are directed toward flexible leafletvalve devices in which the base of each leaflet forms a straight line.

A prosthetic valve is provided comprising a leaflet frame and aplurality of leaflets coupled to the leaflet frame. Each leafletincludes a free edge and a leaflet base. Each leaflet has a planar zonein a central region, wherein the planar zone is substantially planar.The planar zone defines a shape having an area, wherein the area islarger nearer the base than the free edge. The leaflet is operable tobend about a straight base segment of the leaflet base in which theplanar zone base of the planar zone of the leaflet is a straight linethat has a length of less than C.

A method of forming a prosthetic heart valve, comprises: providing aleaflet frame having a generally tubular shape, the leaflet framedefining a plurality of leaflet windows wherein each of the leafletwindows includes two leaflet window sides, a leaflet window base, and aleaflet window top; providing a film; wrapping the film about theleaflet frame bringing more than one layer of the film into contact withadditional layers of the film defining at least one leaflet extendingfrom each of the leaflet windows; and bonding the layers of film toitself and to the leaflet frame, wherein each leaflet has substantiallya shape of an isosceles trapezoid having two leaflet sides, a leafletbase and a free edge opposite the leaflet base, wherein the two leafletsides diverge from the leaflet base, wherein the leaflet base issubstantially flat, wherein the leaflet base is coupled to the windowbase and wherein each of the two leaflet sides are coupled to one of thetwo window sides providing a generally annular support structure, eachleaflet having a planar zone in a central region, wherein the planarzone is substantially planar, wherein the planar zone defines a shapehaving an area, wherein the area is larger nearer the base than the freeedge, wherein the leaflet is operable to bend about a straight basesegment of the leaflet base in which the planar zone base of the planarzone of the leaflet is a straight line that has a length of less than C.

In some embodiments, particularly in the case of transcatheter valves,the leaflet frame is placed coaxially within an outer frame. In theseembodiments the leaflet frame and the outer frame act in concert as thediameter is reduced for delivery, and then re-expanded at the recipientsite.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are included to provide a furtherunderstanding of the present disclosure and are incorporated in andconstitute a part of this specification, illustrate embodimentsdescribed herein, and together with the description serve to explain theprinciples discussed in this disclosure.

FIG. 1A is a side view of an embodiment of a valve;

FIG. 1B is a side view of the embodiment of the valve of FIG. 1A;

FIG. 1C is a perspective view of the embodiment of the valve of FIG. 1A;

FIG. 1D is a representation of a valve in an expanded configuration;

FIG. 1E is a representation of a valve in a compressed configuration;

FIG. 2A is a representation of the embodiment of the valve of FIG. 1Aunrolled to a flat orientation;

FIG. 2B is an exploded representation of the embodiment of the valve ofFIG. 1A unrolled to a flat orientation;

FIG. 3A is an axial or top view of the embodiment of the valve of FIG.1A in an open configuration;

FIG. 3B is an axial or top view of the embodiment of the valve of FIG.1A in a closed configuration;

FIG. 4A is a side view of an embodiment of a transcatheter deliverysystem within anatomy;

FIG. 4B is a side view of an embodiment of a surgical valve withinanatomy;

FIG. 5A is a cross-sectional view of an embodiment of the valve duringmanufacture;

FIG. 5B is a cross-sectional view of an embodiment of the valve;

FIG. 6A is a representation of an embodiment of an outer frame unrolledto a flat orientation;

FIG. 6B is a representation of an embodiment of an outer frame unrolledto a flat orientation;

FIG. 7A is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 7B is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8A is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8B is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8C is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8D is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8E is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 8F is a representation of an embodiment of a leaflet frame unrolledto a flat orientation;

FIG. 9A is a side view of valve components on an assembly mandrel, inaccordance with an embodiment;

FIG. 9B is a side view of valve components on an assembly mandrel, inaccordance with an embodiment;

FIG. 10A is a side exploded view of a prosthetic valve comprising aleaflet frame having a generally tubular shape and an outer frame havinga generally tubular shape that are coupled by a mechanic engagementmember, in accordance with another embodiment;

FIG. 10B is an assembled view of the embodiment of FIG. 10A;

FIG. 11A is a side view of an embodiment of a valve;

FIG. 11B is a top view of the embodiment of the valve of FIG. 1A;

FIG. 12 is a side view of a leaflet frame on an assembly mandrel, inaccordance with an embodiment;

FIG. 13A is a side view of the leaflet frame on a cutting mandrel, inaccordance with an embodiment;

FIG. 13B is a perspective view of the leaflet frame on the cuttingmandrel of FIG. 13A; and

FIGS. 14A and 14B are simplified top view representations of a heartvalve having three leaflets, in closed and open positions, respectively.

DETAILED DESCRIPTION

Persons skilled in the art will readily appreciate that various aspectsof the present disclosure can be realized by any number of methods andapparatus configured to perform the intended functions. Stateddifferently, other methods and apparatuses can be incorporated herein toperform the intended functions. It should also be noted that theaccompanying drawing figures referred to herein are not necessarilydrawn to scale, but may be exaggerated to illustrate various aspects ofthe present disclosure, and in that regard, the drawing figures shouldnot be construed as limiting.

Although the embodiments herein may be described in connection withvarious principles and beliefs, the described embodiments should not bebound by theory. For example, embodiments are described herein inconnection with prosthetic valves, more specifically cardiac prostheticvalves. However, embodiments within the scope of this disclosure can beapplied toward any valve or mechanism of similar structure and/orfunction. Furthermore, embodiments within the scope of this disclosurecan be applied in non-cardiac applications.

The term leaflet as used herein in the context of prosthetic valves is acomponent of a one-way valve wherein the leaflet is operable to movebetween an open and closed position under the influence of a pressuredifferential. In an open position, the leaflet allows blood to flowthrough the valve. In a closed position, the leaflet substantiallyblocks retrograde flow through the valve. In embodiments comprisingmultiple leaflets, each leaflet cooperates with at least one neighboringleaflet to block the retrograde flow of blood. The pressure differentialin the blood is caused, for example, by the contraction of a ventricleor atrium of the heart, such pressure differential typically resultingfrom a fluid pressure building up on one side of the leaflets whenclosed. As the pressure on an inflow side of the valve rises above thepressure on the outflow side of the valve, the leaflets opens and bloodflows therethrough. As blood flows through the valve into a neighboringchamber or blood vessel, the pressure on the inflow side equalizes withthe pressure on the outflow side. As the pressure on the outflow side ofthe valve raises above the blood pressure on the inflow side of thevalve, the leaflet returns to the closed position generally preventingretrograde flow of blood through the valve.

The term membrane as used herein refers to a sheet of materialcomprising a single composition, such as, but not limited to, expandedfluoropolymer.

The term composite material as used herein refers to a combination of amembrane, such as, but not limited to, expanded fluoropolymer, and anelastomer, such as, but not limited to, a fluoroelastomer. The elastomermay be imbibed within a porous structure of the membrane, coated on oneor both sides of the membrane, or a combination of coated on and imbibedwithin the membrane.

The term laminate as used herein refers to multiple layers of membrane,composite material, or other materials, such as elastomer, andcombinations thereof.

The term film as used herein generically refers to one or more of themembrane, composite material, or laminate.

The term biocompatible material as used herein generically refers to afilm or a biological material, such as, but not limited to, bovinepericardium.

The term leaflet window is defined as that space that a frame definesfrom which a leaflet extends. The leaflet may extend from frame elementsor adjacent to frame elements and spaced apart therefrom.

The terms native valve orifice and tissue orifice refer to an anatomicalstructure into which a prosthetic valve may be placed. Such anatomicalstructure includes, but is not limited to, a location wherein a cardiacvalve may or may not have been surgically removed. It is understood thatother anatomical structures that may receive a prosthetic valve include,but are not limited to, veins, arteries, ducts and shunts. Althoughreference is made herein to replacing a native valve with a prostheticvalve, it is understood and appreciated that a valve orifice or implantsite may also refer to a location in a synthetic or biological conduitthat may receive a valve for a particular purpose, and therefore thescope of the embodiments provided herein is not limited to valvereplacement.

As used herein, “couple” means to join, connect, attach, adhere, affix,or bond, whether directly or indirectly, and whether permanently ortemporarily.

Embodiments herein include various apparatus, systems, and methods for aprosthetic valve suitable for surgical and transcatheter placement, suchas, but not limited to, cardiac valve replacement. The valve is operableas a one-way valve wherein the valve defines a valve orifice into whichleaflets open to permit flow and close so as to occlude the valveorifice and prevent flow in response to differential fluid pressure.

Embodiments provided herein are related to controlled leaflet opening.The durability of the valve leaflets is largely controlled by thecharacter of bending exhibited by the leaflet during the opening-closingcycle. Small radius bends, creases and particularly intersectingcreases, can produce high stress zones in the leaflet. These high stresszones can cause the formation of holes and tears under repetitiveloading.

Controlled bending is of particular importance in thin, high-modulussynthetic leaflets, since the bending in these materials tends to becellophane-like. If the leaflet bending character is uncontrolled, notonly do creases form, but crease intersections lead to formation oflarge three dimensional structures that oppose bending and slow down theleaflet motion, both in opening and closing: in order to avoid this, thesequence of opening of the parts of the leaflet must be controlled.

In accordance with some embodiments presented herein, a prosthetic valvecomprises two frames; a leaflet frame and an outer frame. The film thatcomprises the leaflet may be coupled to the inner surface of the leafletframe. In some other embodiments, the film that comprises the leaflet iscontained between the leaflet frame and the outer frame and extendsthrough a leaflet window defined by the leaflet frame. The leaflet,therefore, is significantly prevented from peeling or delaminating as itis contained between the leaflet frame and outer frame, as compared towhere the leaflets are only coupled to the inner surface of the leafletframe.

In accordance with some embodiments presented herein, a prosthetic valvecomprises two frames; a leaflet frame and an outer frame. The leafletframe and the outer frame are separated from each other by a film. Inother words, there is a metal to polymer to metal interconnection,wherein there is no metal to metal contact between the two frames.

In accordance with some embodiments presented herein, a prosthetic valvecomprises two frames; a leaflet frame and an outer frame. The leafletframe is nested within the outer frame, wherein the leaflet frame andouter frame cooperate to provide relatively high resistance to flatplate compression, among other things. In accordance with someembodiments, the outer frame provides frame elements that overlay theleaflet windows that are defined by the leaflet frame so as to providestructural support over the leaflet windows. In accordance with someembodiments, the outer frame provides frame elements that overlay theleaflet windows that are defined by the leaflet frame so as to preventtissue from extending into the leaflet windows when implanted. Inaccordance with some embodiments, the outer frame provides frameelements that overlay the leaflet windows that are defined by theleaflet frame and act in concert so as to allow the frame assembly tocompress and expand uniformly for transcatheter embodiments.

In accordance with some embodiments presented herein, a prosthetic valvecomprises two frames; a leaflet frame and an outer frame. The leafletframe defines leaflet windows that define, in part, the shape of theleaflets. In some embodiments the leaflet comprises a flat base, whereinthe leaflet bends from the base towards the free edge with minimalcreasing and fluttering. In accordance with embodiments, the leafletcomprises a flat base, that, among other things, provides for one ormore of a shorter valve length, substantially prevents blood stagnationand pooling and encourages washing at the base, as compared to leafletshaving a rounded base.

In accordance with some embodiments presented herein, a prosthetic valvecomprises two frames; a leaflet frame and an outer frame. The leafletframe defines leaflet windows from which the leaflets extend. Theleaflets are defined by the intersection of films that form anoverlapping zone so as to define, at least in part, the leaflet baseand/or the leaflet sides.

Embodiments provided herein address controlled leaflet opening. Thedurability of the valve leaflets is largely controlled by the characterof bending exhibited by the leaflet during the opening-closing cycle.Small radius bends, creases and particularly intersecting creases, canproduce high stress zones in the leaflet. These high stress zones cancause the formation of holes and tears under repetitive loading.Embodiments provided herein provide a feature of leaflet shape so as tominimize crease formation, which is of particular importance in thin,high-modulus leaflets, since the bending in these materials tends to becellophane-like. If the leaflet bending is unrestricted, not only docreases form, but crease intersections lead to formation of large threedimensional structures that oppose bending and slow down the leafletmotion, both in opening and closing.

Valve

FIGS. 14A and 14B are simplified top view representations of a valve 100having three leaflets 140, in closed and open positions, respectively.The leaflets 140 have a free edge 142 and a leaflet base 143. Theleaflet base 143 is defined, at least in part, by where the leaflet 140bends when it is open.

In any trileaflet valve 100, each leaflet 140 occupies a segment 196 ofa circle 195 defined by a leaflet frame 130, as shown in FIG. 3A. Thevalve 100 is symmetric so that angle θ is 120° and arc length S is ⅓ ofthe diameter of the circle 195.

In certain configurations bending of the leaflet 140 may occur alongchord C. Chord C is defined as a straight line that extends from twocommissure posts 132. Leaflet actuation in this case is rapid, but thetotal flow area is restricted to a small equilateral triangle with sidesof length R providing less than optimal flow area leading to excessiverestriction.

In certain other configurations, bending of the leaflet 140 may occuralong arc length S, at least for high-modulus, thin materials, ifbending of the leaflet base 143 occurs close to the leaflet frame 130essentially along the circle 195. In such cases the closing action ofthe leaflet 140 is delayed when flow is reversed.

In accordance with embodiments provided herein, for optimum performanceof the leaflet 140, it is appreciated herein that bending of the leaflet140 adjacent the leaflet base 143 must be along a substantially straightline instead of an arc, but this straight line has a length that must beless than a length of chord C. This straight line is represented by astraight base segment 145 in FIG. 14A.

In embodiments of prosthetic valves 100 provided herein, each of theleaflets 140 comprises a leaflet base 143 having a flat portion 149 thatdefines a shelf structure, as shown in FIG. 14A. In operation, theleaflet 140 bends from the flat portion 149 along the straight basesegment 145 of the leaflet base 143 towards the free edge 142 withminimal creasing and fluttering. The leaflet base 143 having a flatportion 149 provides, among other things, a shorter valve length,substantially prevents blood stagnation and pooling and encourageswashing at the leaflet base 143, as compared to leaflets 140 having arounded leaflet base 143. A leaflet base 143 that has a straight basesegment 145 also provides a superior hemodynamic outcome during theclosing phase of the valve.

In accordance with embodiments of the prosthetic valve 100 providedherein, a planar zone 192 of the leaflet 140 comprises a planar zonebase 193 which is coincident with the straight base segment 145 which isa substantially straight line that has a length that is less than alength of chord C. This combination produces basal bending of theleaflet 140.

FIG. 1A is a side view of a valve 100, in accordance with an embodiment.FIG. 1B is also a side view of the valve 100 of FIG. 1A rotated 60degrees about the longitudinal axis X. FIG. 1C is a perspective view ofthe valve 100 of FIG. 1A. FIG. 11A is a side view of another embodimentof a valve 100. FIG. 11B is a perspective view of the embodiment of thevalve of FIG. 11A. FIGS. 3A and 3B are axial views of the valve 100 ofFIG. 1A, in an open and closed configuration, respectively, whichpresents a configuration substantially the same as for the valve 100 ofthe embodiment of FIG. 11A. It is shown that bending of the leaflet 140occurs at the leaflet base 143, a portion of which is along a straightbase segment 145. In FIGS. 1C, 3B and 11B, the leaflets 140 are shownslightly open to better show the features but it is understood that afully closed valve 100 will have the free edges 142 of the leaflets 140coming together to coapt under the influence of downstream fluidpressure which results in closing the valve to prevent downstream bloodfrom flowing retrograde through the valve.

FIG. 1A is a side view of a valve 100, in accordance with an embodiment.FIG. 1B is also a side view of the valve 100 of FIG. 1A rotated 60degrees about the longitudinal axis X. FIG. 1C is a perspective view ofthe valve 100 of FIG. 1A. FIG. 2A is a side view of the valve 100 ofFIG. 1A wherein the valve 100 has been longitudinally cut and laid opento better illustrate the elements of the generally tubular-shaped valve100. FIG. 2B is an exploded view of the embodiment of FIG. 2A. FIGS. 3Aand 3B are axial views of the valve 100 of FIG. 1A in an open and closedconfiguration, respectively. The valve 100 of the embodiment of FIG. 1Ais suitable for surgical or transcatheter delivery and deployment. Aswill be explained below, the valve 100 is operable to be reduced indiameter for transcatheter delivery and radially expanded fordeployment.

Referring again to the embodiment of the valve 100 of FIG. 1A, the valve100 comprises an outer frame 120, a leaflet frame 130, and a film 160covering the outer frame 120 and leaflet frame 130, coupling the outerframe 120 to the leaflet frame 130, and defining leaflets 140. Theembodiment of valve 100 is discussed further related to a transcathetervalve that may be compressed and re-expanded. It is understood that theembodiment of valve 100 is also applicable to a surgical valve by theaddition of a sewing cuff 171 as shown in FIG. 4B. Leaflet frame andouter frame configurations related to surgical valve only embodimentswhere the valves have a fixed diameter, will be discussed in otherembodiments later in this disclosure.

FIG. 11A is a side view of another embodiment of a valve 100. FIG. 11Bis a perspective view of the embodiment of the valve of FIG. 11A. Thevalve 100 of the embodiment of FIG. 11A is suitable for surgicalplacement. As will be explained below, the valve 100 is operable toretain a predetermined diameter that resists radial compression orexpansion. Referring again to the embodiment of the valve 100 of FIG.11A, the valve 100 comprises a leaflet frame 130, and a film 160covering the leaflet frame 130 and defining leaflets 140.

The embodiments of the valve 100 of FIGS. 1A and 11A are provided asnon-limiting examples to show that the concepts presented herein relatedto leaflets with straight line basal bending about a straight basesegment of the leaflet in which the planar zone base of the planar zoneof the leaflet is a line of length less than chord C, may be applied toprosthetic heart valves of many configurations and designs.

Outer Frame

The embodiment of the valve 100 of FIG. 1A comprises a leaflet frame 130and an outer frame 120. The outer frame 120 is a generally tubularmember defining a generally open pattern of apertures 122, in accordancewith an embodiment. In accordance with transcatheter embodiments, theouter frame 120 is operable to allow the outer frame 120 to becompressed and expanded between different diameters. The outer frame 120comprises an outer frame first end 121 a and an outer frame second end121 b opposite the outer frame first end 121 a. The outer frame 120comprises an outer frame outer surface 126 a and an outer frame innersurface 126 b opposite the outer frame outer surface 126 a, as shown inFIG. 5A. The outer frame 120 may comprise a structure known in the artas a stent. A stent is a tubular member that may have a small diametersuitable for percutaneous transcatheter delivery into the anatomy, andmay be expanded to a larger diameter when deployed into the anatomy.Stents having various designs and material properties are well known inthe art.

By way of example, and as illustrated in the embodiments of FIGS. 1A-1Cand 2A-2B, the valve 100 includes the outer frame 120 that defines astent having apertures 122 having generally a diamond shape when in alarge diameter configuration, as shown generally in FIG. 1D. Uponcompression to a smaller diameter, the apertures 122 deform to generallydefine an elongated diamond shape, as shown generally in FIG. 1E. Uponre-expansion to a larger diameter, the apertures 122 re-expand to againdefine a generally diamond shape.

FIGS. 6A and 6B are side views of alternative embodiments of the outerframe 120 a, 120 b wherein the outer frame has been longitudinally cutand laid open to better illustrate the elements of the outer frame. Itis appreciated that there are many embodiments of the outer frame havingconfigurations suitable for the particular purpose.

An open framework of the stent can define any number of features,repeatable or otherwise, such as geometric shapes and/or linear ormeandering series of sinusoids. Geometric shapes can comprise any shapethat facilitates substantially uniform circumferential compression andexpansion. The outer frame 120 may comprise a cut tube, or any otherelement suitable for the particular purpose. The outer frame 120 may beetched, cut, laser cut, or stamped into a tube or a sheet of material,with the sheet then formed into a substantially cylindrical structure.Alternatively, an elongated material, such as a wire, bendable strip, ora series thereof, can be bent or braided and formed into a substantiallycylindrical structure wherein the walls of the cylinder comprise an openframework that is compressible to a smaller diameter in a generallyuniform and circumferential manner and expandable to a larger diameter.

It is known that stents of various designs may be elastically deformableso as to be self-expanding under spring loads. It is also known thatstents of various designs may be plastically deformable so as to bemechanically expanded such as with a balloon. It is also known thatstents of various designs may be plastically deformable as well aselastically deformable. The embodiments of the outer frame 120 presentedherein are not to be limited to a specific stent design or mode ofexpansion.

The outer frame 120 can comprise any metallic or polymeric biocompatiblematerial. For example, the outer frame 120 can comprise a material, suchas, but not limited to nitinol, cobalt-nickel alloy, stainless steel, orpolypropylene, acetyl homopolymer, acetyl copolymer, ePTFE, other alloysor polymers, or any other biocompatible material having adequatephysical and mechanical properties to function as described herein.

In accordance with embodiments, the outer frame 120 and/or leaflet frame130 can be configured to provide positive engagement with an implantsite to firmly anchor the valve 100 to the site, as shown in FIG. 4Arepresenting a transcatheter deployment of the valve 100. In accordancewith an embodiment, the outer frame 120 can comprise a sufficientlyrigid frame having small elastic recoil so as to maintain sufficientapposition against a tissue orifice 150 to maintain position. Inaccordance with another embodiment, the outer frame 120 and/or leafletframe 130 can be configured to expand to a diameter that is larger thana tissue orifice 150 so that when valve 100 expands into the tissueorifice 150, it can be firmly seated therein. In accordance with anotherembodiment, the outer frame 120 can comprise one or more anchors (notshown) configured to engage the implant site, such as a tissue orifice150, to secure the valve 100 to the implant site.

It is appreciated that other elements or means for coupling the valve100 to an implant site are anticipated. By way of example, but notlimited thereto, other means, such as mechanical and adhesive means maybe used to couple the valve 100 to a synthetic or biological conduit.

Sewing Cuff

In accordance with a surgical valve 100 embodiment, the valve 100further comprises a sewing cuff 171 about an outer frame outer surface127 in accordance with an embodiment, as shown in FIG. 4B, or about theleaflet frame 130 in embodiments where there is not outer frame 120. Thesewing cuff 171 is operable to provide structure that receives suturefor coupling to the implant site. The sewing cuff 171 may comprise anysuitable material, such as, but not limited to, double velour polyester.The sewing cuff 171 may be located circumferentially around a perimeterof the outer frame 120 or the leaflet frame 130 if there is no outerframe 120. Sewing cuffs 171 are known in the art.

Leaflet Frame

Referring again to FIGS. 1C and 2B, the leaflet frame 130 of theembodiment of FIG. 1C, is a generally tubular member defining aplurality of leaflet windows 137 coupled together by connecting elements139, in accordance with an embodiment. The leaflet frame 130 comprises aleaflet frame first end 138 a and a leaflet frame second end 138 bopposite the leaflet frame first end 138 a. The leaflet frame 130comprises a leaflet frame outer surface 132 a and a leaflet frame innersurface 132 b opposite the leaflet frame outer surface 132 a, as shownin FIG. 5A. The leaflet frame first end 138 a and the leaflet framesecond end 138 b define a generally zigzag configuration to facilitateflexion about flex points 136 such as which facilitates compression andexpansion between different diameters for compression onto a deliverydevice and expansion by a balloon for the transcatheter valve 100embodiments, as generally explained for the outer frame 120. As will bediscussed later, the surgical valve 100 embodiment may or may not havethe zigzag configuration since the surgical valve 100 may be of a fixeddiameter and need not be operable to compress and re-expand.

The leaflet frame 130 may be referred to in a general sense as a stentor a frame.

The leaflet frame 130 defines a predetermined repeating pattern as shownin FIG. 2B, in accordance with an embodiment. The leaflet frame 130defines three interconnected leaflet windows 137 having a substantiallytriangular shape. Each of the leaflet windows 137 includes two leafletwindow sides 133 including commissure posts 132, a leaflet window base134, and a leaflet window top 135. In this embodiment, the leafletwindow base 134 defines a flex point 136 which will be described furtherbelow. A leaflet window side 133 and leaflet window top 135 of oneleaflet window 137 is interconnected with a leaflet window side 133 ofan adjacent leaflet window 137 at the commissure posts 132.

The leaflet frame 130 defines any number of features and geometricshapes that facilitate substantially uniform circumferential compressionand expansion. The leaflet frame 130 may comprise a cut tube, or anyother element suitable for the particular purpose. The leaflet frame 130may be etched, cut, laser cut, or stamped into a tube or a sheet ofmaterial, with the sheet then formed into a substantially cylindricalstructure. Alternatively, an elongated material, such as a wire,bendable strip, or a series thereof, can be bent or braided and formedinto a substantially cylindrical structure wherein the walls of thecylinder comprise an open framework that is compressible to a smallerdiameter in a generally uniform and circumferential manner andexpandable to a larger diameter.

The leaflet frame 130 can comprise any metallic or polymericbiocompatible material. For example, the leaflet frame 130 can comprisea material, such as, but not limited to nitinol, cobalt-nickel alloy,stainless steel, or polypropylene, acetyl homopolymer, acetyl copolymer,ePTFE, other alloys or polymers, or any other biocompatible materialhaving adequate physical and mechanical properties to function asdescribed herein.

As will be described in more detail below, a film 160 is disposed overeach of the three leaflet windows 137 to form a leaflet 140. Furtherembodiments will be described below wherein the leaflet window 137defines shapes other than a substantially triangular shape, including,but not limited to a parabolic shape and a trapezoidal shape, with andwithout a leaflet window top 135, suitable for a particular purpose ofan embodiment of a surgical and transcatheter valve 100.

FIGS. 7A and 7B are side views of alternative embodiments of the leafletframe 130 a, 130 b wherein the leaflet frame has been longitudinally cutand laid open to better illustrate the elements of the leaflet frame.The leaflet frame 130 a includes leaflet windows 137 a having asubstantially triangular shape defining a pointed leaflet window base134 a. The leaflet frame 130 b includes leaflet windows 137 b having asubstantially triangular shape defining a flat leaflet window base 134b. The flat leaflet window base 134 b may be used to define the leafletbase.

FIGS. 8A-8C are side views of alternative embodiments of the leafletframe 130 c-130 e wherein the leaflet frame has been longitudinally cutand laid open to better illustrate the elements of the leaflet frame.The leaflet frame 130 c includes leaflet windows 137 c having asubstantially triangular shape defining a pointed leaflet window base134 c. The leaflet frame 130 d includes leaflet windows 137 d having asubstantially parabolic shape defining a rounded leaflet window base 134d. The flat leaflet window base 134 b may be used to define the leafletbase. The leaflet frame 130 e includes leaflet windows 137 e having asubstantially triangular shape defining a pointed leaflet window base134 e but not having a leaflet window top.

FIG. 8D is a side view of an alternative embodiment of the leaflet frame130 f wherein the leaflet frame 130 f has been longitudinally cut andlaid open to better illustrate the elements of the leaflet frame. Theleaflet frame 130 f includes leaflet windows 137 f having asubstantially isosceles trapezoid shape defining a flat leaflet windowbase 134 f. The flat leaflet window base 134 f may be used to define theleaflet base. A leaflet 140 f is shown in dashed line to represent wherethe leaflet 143 f is located within the leaflet window 137 f, theleaflet window 137 f being defined by the leaflet window sides 133 f andthe leaflet window base 134 f. In accordance with other embodiments ofthe prosthetic valve, each leaflet 140 f has substantially the shape ofan isosceles trapezoid having two leaflet sides 141 f, a leaflet base143 f and a free edge 142 f opposite the leaflet base 143 f, wherein thetwo leaflet sides 141 f diverge from the leaflet base 143 f, wherein theleaflet base 143 f is substantially flat, as shown in dashed lines inFIG. 8D. The leaflet frame 130 f further comprises extension elements1121 that may be used to provide additional coaptation of the leafletfree edges.

FIG. 8E is a side view of an alternative embodiment of the leaflet frame130 g wherein the leaflet frame 130 g has been longitudinally cut andlaid open to better illustrate the elements of the leaflet frame. Theleaflet frame 130 g includes leaflet windows 137 g having asubstantially isosceles trapezoid shape defining a flat leaflet windowbase 134 f. The flat leaflet window base 134 g may be used to define theleaflet base. A leaflet 140 g is shown in dashed line to represent wherethe leaflet 140 g is located within the leaflet window 137 g. Inaccordance with other embodiments of the prosthetic valve, each leaflet140 g has substantially the shape of an isosceles trapezoid having twoleaflet sides 141 g, a leaflet base 142 g and a free edge 143 g oppositethe leaflet base, wherein the two leaflet sides 141 g diverge from theleaflet base 143 f, wherein the leaflet base 143 f is substantiallyflat, as shown in dashed lines in FIG. 8E.

FIG. 8F is a side view of an alternative embodiment of the leaflet frame130 h wherein the leaflet frame 130 h has been longitudinally cut andlaid open to better illustrate the elements of the leaflet frame 130 h.The leaflet frame 130 h comprises a base element 138 h and a pluralityof spaced apart spade elements 170 interconnected by the base element138 h. Each leaflet window 137 h is defined by a spade side 175 of onespade element 170 and a side 175 of an adjacent spade element 170, andwherein each leaflet window base 134 h is defined by the base element138 h. In accordance with an embodiment of the prosthetic valve, eachleaflet 140 h has substantially the shape of an isosceles trapezoidhaving two leaflet sides 141 h, a leaflet base 142 h and a free edge 143h opposite the leaflet base 142 h, wherein the two leaflet sides 141 hdiverge from the leaflet base 142 h, wherein the leaflet base 142 h issubstantially flat, as shown in dashed lines in FIG. 8F. It is notedthat at least a portion of the leaflet side 141 h is supported by theleaflet frame 130 h at the spade side 175 and at least a portion of theleaflet side 141 h between the spade side 175 and the leaflet windowbase 134 h is not supported by the leaflet frame 130 h.

As previously discussed, the leaflet window base may be used to definethe leaflet base in accordance with embodiments. Also as previouslydiscussed, the leaflet base may be defined as a virtual leaflet base1033 by a fold line 147 in the film 160 spaced apart from the leafletwindow base 134, as shown in FIG. 2B. It is appreciated that there aremany embodiments of the outer frame 120 having configurations suitablefor the particular purpose.

In valve 100 embodiments suitable for transcatheter placement, theleaflet frame 130 is elastically, plastically, or both, compressible toobtain a relatively small diameter to accommodate percutaneoustranscatheter mounting and delivery. In accordance with an embodiment asshown in FIG. 2B, the leaflet frame 130 may comprise one or more flexpoints 136 so as to provide a preferential flexing location for theleaflet frame 130 to flex when compressed to a smaller diameter. A flexpoint 136 comprises a site on the leaflet frame 130 that undergoes thehighest degree of bending when transitioning from an expanded state tocollapsed state and vice versa. The flex point 136 can comprise ageometry, structural modification or material modification, amongothers, that biases the leaflet frame 130 to bend at the flex point 136when compressed.

The leaflet frame 130 may comprise, such as, but not limited to, anyelastically deformable metallic or polymeric biocompatible material, inaccordance with embodiments. The leaflet frame 130 may comprise ashape-memory material, such as nitinol, a nickel-titanium alloy. Othermaterials suitable for the leaflet frame 130 include, but are notlimited to, other titanium alloys, stainless steel, cobalt-nickel alloy,polypropylene, acetyl homopolymer, acetyl copolymer, other alloys orpolymers, or any other biocompatible material having adequate physicaland mechanical properties to function as a leaflet frame 130 asdescribed herein.

In accordance with an embodiment, the leaflet frame 130 and the outerframe 120 comprise a shape memory material operable to flex under loadand retain its original shape when the load is removed, thus allowingthe leaflet frame 130 and the outer frame 120 to self-expand from acompressed shape to a predetermined shape. The leaflet frame 130 and theouter frame 120 may comprise the same or different materials. Inaccordance with an embodiment, the leaflet frame 130 and the outer frame120 are plastically deformable to be expanded by a balloon. In anotherembodiment the outer frame 120 and the leaflet frame 130 are elasticallydeformable so as to be self-expanding.

Film

The film 160 is generally any sheet-like material that is biologicallycompatible and configured to couple to the outer frame 120 and theleaflet frame 130, in accordance with embodiments. It is understood thatthe term “film” is used generically for one or more biocompatiblematerials suitable for a particular purpose. The leaflets 140 are alsocomprised of the film 160.

In accordance with an embodiment, the biocompatible material is a film160 that is not of a biological source and that is sufficiently flexibleand strong for the particular purpose, such as a biocompatible polymer.In an embodiment, the film 160 comprises a biocompatible polymer that iscombined with an elastomer, referred to as a composite.

It is also understood that the film 160 coupled to the outer frame 120may not be the same film 160 coupled to the leaflet frame 130, inaccordance with embodiments. Details of various types of film 160 arediscussed below. In an embodiment, the film 160 may be formed from agenerally tubular material to at least partially cover the outer frame120 and the leaflet frame 130. The film 160 can comprise one or more ofa membrane, composite material, or laminate. Details of various types offilm 160 are discussed below.

In an embodiment, the film 160 comprises a biocompatible polymer that iscombined with an elastomer, referred to as a composite. A materialaccording to one embodiment includes a composite material comprising anexpanded fluoropolymer membrane, which comprises a plurality of spaceswithin a matrix of fibrils, and an elastomeric material. It should beappreciated that multiple types of fluoropolymer membranes and multipletypes of elastomeric materials can be combined to form a laminate whileremaining within the scope of the present disclosure. It should also beappreciated that the elastomeric material can include multipleelastomers, multiple types of non-elastomeric components, such asinorganic fillers, therapeutic agents, radiopaque markers, and the likewhile remaining within the scope of the present disclosure.

In accordance with an embodiment, the composite material includes anexpanded fluoropolymer material made from porous ePTFE membrane, forinstance as generally described in U.S. Pat. No. 7,306,729 to Bacino.

The expandable fluoropolymer, used to form the expanded fluoropolymermaterial described, may comprise PTFE homopolymer. In alternativeembodiments, blends of PTFE, expandable modified PTFE and/or expandedcopolymers of PTFE may be used. Non-limiting examples of suitablefluoropolymer materials are described in, for example, U.S. Pat. No.5,708,044, to Branca, U.S. Pat. No. 6,541,589, to Baillie, U.S. Pat. No.7,531,611, to Sabol et al., U.S. patent application Ser. No. 11/906,877,to Ford, and U.S. patent application Ser. No. 12/410,050, to Xu et al.

The expanded fluoropolymer membrane can comprise any suitablemicrostructure for achieving the desired leaflet performance. Inaccordance with an embodiment, the expanded fluoropolymer comprises amicrostructure of nodes interconnected by fibrils, such as described inU.S. Pat. No. 3,953,566 to Gore. The fibrils radially extend from thenodes in a plurality of directions, and the membrane has a generallyhomogeneous structure. Membranes having this microstructure maytypically exhibit a ratio of matrix tensile strength in two orthogonaldirections of less than 2, and possibly less than 1.5.

In another embodiment, the expanded fluoropolymer membrane has amicrostructure of substantially only fibrils, as is generally taught byU.S. Pat. No. 7,306,729, to Bacino. The expanded fluoropolymer membranehaving substantially only fibrils, can possess a high surface area, suchas greater than 20 m²/g, or greater than 25 m²/g, and in someembodiments can provide a highly balanced strength material having aproduct of matrix tensile strengths in two orthogonal directions of atleast 1.5×10⁵ MPa², and/or a ratio of matrix tensile strengths in twoorthogonal directions of less than 4, and possibly less than 1.5.

The expanded fluoropolymer membrane can be tailored to have any suitablethickness and mass to achieve the desired leaflet performance. By way ofexample, but not limited thereto, the leaflet 140 comprises an expandedfluoropolymer membrane having a thickness of about 0.1 μm. The expandedfluoropolymer membrane can possess a mass per area of about 1.15 g/m².Membranes according to an embodiment of the invention can have matrixtensile strengths of about 411 MPa in the longitudinal direction and 315MPa in the transverse direction.

Additional materials may be incorporated into the pores or within thematerial of the membranes or in between layers of membranes to enhancedesired properties of the leaflet. Composite materials described hereincan be tailored to have any suitable thickness and mass to achieve thedesired leaflet performance. Composite materials according toembodiments can include fluoropolymer membranes and have a thickness ofabout 1.9 μm and a mass per area of about 4.1 g/m².

The expanded fluoropolymer membrane combined with elastomer to form acomposite material provides the elements of the present disclosure withthe performance attributes required for use in high-cycle flexuralimplant applications, such as heart valve leaflets, in various ways. Forexample, the addition of the elastomer can improve the fatigueperformance of the leaflet by eliminating or reducing the stiffeningobserved with ePTFE-only materials. In addition, it may reduce thelikelihood that the material will undergo permanent set deformation,such as wrinkling or creasing, that could result in compromisedperformance. In one embodiment, the elastomer occupies substantially allof the pore volume or space within the porous structure of the expandedfluoropolymer membrane. In another embodiment the elastomer is presentin substantially all of the pores of the at least one fluoropolymerlayer. Having elastomer filling the pore volume or present insubstantially all of the pores reduces the space in which foreignmaterials can be undesirably incorporated into the composite. An exampleof such foreign material is calcium that may be drawn into the membranefrom contact with the blood. If calcium becomes incorporated into thecomposite material, as used in a heart valve leaflet, for example,mechanical damage can occur during cycling open and closed, thus leadingto the formation of holes in the leaflet and degradation inhemodynamics.

In an embodiment, the elastomer that is combined with the ePTFE is athermoplastic copolymer of tetrafluoroethylene (TFE) and perfluoromethylvinyl ether (PMVE), such as described in U.S. Pat. No. 7,462,675 toChang et al. As discussed above, the elastomer is combined with theexpanded fluoropolymer membrane such that the elastomer occupiessubstantially all of the void space or pores within the expandedfluoropolymer membrane to form a composite material. This filling of thepores of the expanded fluoropolymer membrane with elastomer can beperformed by a variety of methods. In one embodiment, a method offilling the pores of the expanded fluoropolymer membrane includes thesteps of dissolving the elastomer in a solvent suitable to create asolution with a viscosity and surface tension that is appropriate topartially or fully flow into the pores of the expanded fluoropolymermembrane and allow the solvent to evaporate, leaving the filler behind.

In one embodiment, the composite material comprises three layers: twoouter layers of ePTFE and an inner layer of a fluoroelastomer disposedtherebetween. Additional fluoroelastomers can be suitable and aredescribed in U.S. Publication No. 2004/0024448 to Chang et al.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of delivering the filler via adispersion to partially or fully fill the pores of the expandedfluoropolymer membrane.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of bringing the porousexpanded fluoropolymer membrane into contact with a sheet of theelastomer under conditions of heat and/or pressure that allow elastomerto flow into the pores of the expanded fluoropolymer membrane.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of polymerizing the elastomerwithin the pores of the expanded fluoropolymer membrane by first fillingthe pores with a prepolymer of the elastomer and then at least partiallycuring the elastomer.

After reaching a minimum percent by weight of elastomer, the leafletsconstructed from fluoropolymer materials or ePTFE generally performedbetter with increasing percentages of elastomer resulting insignificantly increased cycle lives. In one embodiment, the elastomercombined with the ePTFE is a thermoplastic copolymer oftetrafluoroethylene and perfluoromethyl vinyl ether, such as describedin U.S. Pat. No. 7,462,675 to Chang et al., and other references thatwould be known to those of skill in the art. Other biocompatiblepolymers which can be suitable for use in leaflet 140 include but arenot limited to the groups of urethanes, silicones(organopolysiloxanes),copolymers of silicon-urethane, styrene/isobutylene copolymers,polyisobutylene, polyethylene-co-poly(vinyl acetate), polyestercopolymers, nylon copolymers, fluorinated hydrocarbon polymers andcopolymers or mixtures of each of the foregoing.

Leaflet

Each leaflet window 137 is provided with a biocompatible material, suchas a film 160, which is coupled to a portion of the leaflet window sides133 with the film 160 defining a leaflet 140. Each leaflet 140 defines afree edge 142 and a leaflet base 143, in accordance with an embodiment.As will be described below, it is anticipated that a plurality ofembodiments of leaflet base configurations may be provided. Inaccordance with an embodiment, the film 160 is coupled to a portion ofthe leaflet window sides 133 and to the leaflet window base 134 wherethe leaflet 140 is defined by the portion of the leaflet window sides133 and to the leaflet window base 134. In accordance with anotherembodiment, the film 160 is coupled to a portion of the leaflet windowsides 133 but not the leaflet window base 134 of the leaflet frame 130where the leaflet 140 is defined by the portion of the leaflet windowsides 133 and to a virtual leaflet base 1033 defined in a fold region aswill be described below.

The shape of the leaflets 140 are defined in part by the shape of theleaflet window 137 and the free edge 142. As will be discussed below inaccordance with an embodiment, the shape of the leaflets 140 alsodepends in part on a process that induces a fold at the fold line 147 todefine a virtual leaflet base 1033 as will be described further below,so as to impart a predetermined shape to the leaflet 140. Since highbending stresses are located at the leaflet base, defining a virtualleaflet base 1033 that is not bound by the leaflet window base 134 mayreduce the chance of tearing of the leaflet 140 at the leaflet base143—leaflet window base 134 interface. It may also reduce blood poolingand stagnation at the leaflet base as compared with a rounded leafletbase.

In accordance with an embodiment, substantially the entire leaflet frame130 lies adjacent to the outer frame inner surface 129, as shown in FIG.3A. As such, when the leaflets 140 are in a fully open position, thevalve 100 presents a substantially circular valve orifice 102 as shownin FIG. 3A. Fluid flow is permitted through the valve orifice 102 whenthe leaflets 140 are in an open position.

As the leaflets 140 cycle between the open and closed positions, theleaflets 140 generally flex about the leaflet base 143 and the portionof the leaflet window sides 133 to which the leaflet are coupled. Whenthe valve 100 is closed, generally about half of each free edge 142abuts an adjacent half of a free edge 142 of an adjacent leaflet 140, asshown in FIG. 3B. The three leaflets 140 of the embodiment of FIG. 3Bmeet at a triple point 148. The valve orifice 102 is occluded when theleaflets 140 are in the closed position stopping fluid flow.

Referring to FIG. 3B, in accordance with an embodiment, each leaflet 140includes a central region 182 and two side regions 184 on opposite sidesof the central region 182. The central region 182 is defined by a shapesubstantially that of an isosceles triangle defined by two centralregion sides 183, the leaflet base 143 and the free edge 142. The twocentral region sides 183 converge from the leaflet base 143 to the freeedge 142. Each of the side regions 184 have a shape substantially thatof a triangle and each are defined by one of the central region sides183, one of the leaflet sides 141, and the free edge 142.

In accordance with an embodiment, each of the two side regions 184 andthe central region 182 are substantially planar when the valve 100 is inthe closed position.

The leaflet 140 can be configured to actuate at a pressure differentialin the blood caused, for example, by the contraction of a ventricle oratrium of the heart, such pressure differential typically resulting froma fluid pressure building up on one side of the valve 100 when closed.As the pressure on an inflow side of the valve 100 rises above thepressure on the outflow side of the valve 100, the leaflet 140 opens andblood flows therethrough. As blood flows through the valve 100 into aneighboring chamber or blood vessel, the pressure equalizes. As thepressure on the outflow side of the valve 100 rises above the bloodpressure on the inflow side of the valve 100, the leaflet 140 returns tothe closed position generally preventing the retrograde flow of bloodthrough the inflow side of the valve 100.

It is understood that the leaflet frame 130 may comprise any number ofleaflet windows 137, and thus leaflets 140, suitable for a particularpurpose, in accordance with embodiments. Leaflet frames 130 comprisingone, two, three or more leaflet windows 137 and corresponding leaflets140 are anticipated.

In accordance with embodiments, and referring to FIGS. 3B and 11A, thecentral region 182 is substantially planar, defining a planar zone, whenthe valve 100 is in the closed position and not under fluid pressure.The planar zone has a shape substantially of an isosceles triangle withapices extending to the leaflet frame 130. Referring to FIG. 1D, an apexline La is indicated connecting the apices 147 of the leaflets 140. Theapex line La divides the leaflet 140 into a first region 149 a adjacentthe leaflet frame 130, and a second region 149 b adjacent the free edge142. The first region 149 a contains a larger proportion of planar zone192 than the second region 149 b. In other embodiments, the majority ofthe planar zone 192 of each leaflet 140 is located inferior and exteriorto apex line La joining the apices of two adjacent commissure posts 132.The ratio of area of the planar zone 192 distributed in the first region149 a and second region 149 b has been found produce better leafletopening dynamics than if there were more area of the planar zone 192distributed in the second region 149 b than the first region 149 a.

As shown in the exploded unwrapped view of FIG. 2B of the embodiment ofFIG. 2A, the outer frame 120 is located substantially coplanar,laterally adjacent to and spaced apart from the leaflet frame 130. Theleaflet window base 134 of the leaflet window 137 is located proximateto an outer frame first end 121 a of the outer frame 120 with theleaflet frame first end 138 a of the leaflet frame 130 extending awayfrom the outer frame 120. This placement is also used in the manufactureof the valve 100 as will be discussed below. While in this placement,the film 160 is coupled to the outer frame 120 and a portion of theleaflet frame 130 which couples the outer frame 120 to the leaflet frame130.

The film 160 that spans the space between the outer frame 120 and theleaflet frame 130 defines at least in part a fold region 144. As will bediscussed further below, in accordance with an embodiment, the foldregion 144 is provided to allow the leaflet frame 130 to betelescopically disposed within the outer frame 120, the outer frame 120having an inner diameter that is larger than the outer diameter of theleaflet frame 130, in accordance with an embodiment of a method ofmaking the valve 100, hence creating a fold within the fold region 144along a generally circumferential line 146.

It is anticipated that the film 160 may be coupled to the leaflet frame130 and the outer frame 120 in many ways suitable for a particularpurpose, in accordance with embodiments. In accordance with anembodiment, the outer frame 120 may be wrapped with overlapping layersof a film 160 having a first composition. The leaflet frame 130 may bewrapped with overlapping layers of a film 160 having a secondcomposition. The wrapped leaflet frame 130, the wrapped outer frame 120,and the space between the outer frame 120 and the leaflet frame 130 maybe wrapped with overlapping layers of a film 160 having a thirdcomposition defining, at least in part, the fold region 144.

In another embodiment, the film 160 may be coupled to the inner or outersurface of the leaflet frame 130 and outer frame 120. In anotherembodiment, the film 160 may be coupled to the inner and outer surfaceof the leaflet frame 130 and outer frame 120 sandwiching the leafletframe 130 and outer frame 120 between the film 160. As will be discussedbelow, coupling the film 160 to at least the leaflet frame outer surface132 a and the outer frame inner surface 126 b, as shown in FIGS. 5A-5Bmay provide additional support to the leaflet 140 to preventdisengagement of the leaflet 140 from the leaflet frame 130 since aportion of the film 160 is contained between the leaflet frame 130 andthe outer frame 120, as shown in FIG. 5B.

Wherever the film 160 is present it prevents blood from travelingthrough or across the valve 100 other than through the valve orifice 102when the leaflets 140 are in an open position and uncovered portions ofthe leaflet frame 130 or outer frame 120. As such, the film 160 createsa barrier to blood flow in any interstitial space(s) or apertures 122 ofthe outer frame 120 and leaflet frame 130, and therebetween, that thefilm 160 covers.

The film 160 is fixedly secured or otherwise coupled at a single or aplurality of locations of the inner surface or outer surface of theouter frame 120 and leaflet frame 130, for example, using one or more oftaping, heat shrinking, adhesion and other processes known in the art.In some embodiments, a plurality of membrane/composite layers, i.e., alaminate, are used and can be coupled to both the inner and outersurfaces of the outer frame 120 and the leaflet frame 130 to form atleast a portion of the film 160.

The film 160 comprises any material(s) that have the suitable physicaland mechanical properties to perform the functions described herein. Thefilm 160 may comprise the same material that the leaflet 140 comprisesor a different material. Similarly, the film 160 may or may not behomogenous in material composition. Different portions of the film 160can comprise different materials which can give it different physicaland mechanical properties.

As previously discussed, in an embodiment of a method of making thevalve 100, the leaflet frame 130 is disposed within the outer frame 120in a telescoping manner whereby folding the film 160 in the fold region144, as shown in FIGS. 5A-5B. The leaflet frame 130 is therefore nestedwithin the outer frame 120 while remaining coaxial therewith. Theassembly is further processed to couple the fold region 144 to itselfand to the wrapped leaflet frame 130 and outer frame 120 whilepreventing the film 160 defining the leaflets 140 from adhering tounintended parts of the valve 100 that would prevent leaflet function.

In accordance with another embodiment, the frame members defining theapertures of the leaflet frame 130 and outer frame 120 arepreferentially aligned to provide overlapping and complimentaryarrangement so as to proved structural rigidity to the assembly.

In accordance with an embodiment of a transcatheter valve 100, withreference to FIGS. 1D-1E, the valve 100 may be compressed into acollapsed configuration having a smaller diameter and expanded into anexpanded configuration so that the valve 100 can be endovascularlydelivered in the collapsed configuration and expanded upon deploymentwithin the tissue orifice 150 as shown in FIG. 4 . The leaflet frame 130and the outer frame 120 can be operable to recover circumferentialuniformity when transitioning from the collapsed configuration to theexpanded configuration.

The valve 100 may be mounted onto a delivery catheter, suitable for aparticular purpose. The diameter of the valve 100 in the collapsedconfiguration is determined in part by the thickness of the leafletframe 130 within the outer frame 120 and the leaflet thickness.

Other Considerations

FIGS. 10A and 10B are side exploded and assembled views, respectively,of a prosthetic valve 1000 comprising a leaflet frame 1130 having agenerally tubular shape and an outer frame 1120 having a generallytubular shape that are coupled by a mechanic engagement member 1110, inaccordance with another embodiment. The leaflet frame 1130 comprises anengagement member 1110 operable to engage the outer frame 1120 to affectcoupling in which the leaflet frame 1130 is nested into the outer frame1120 in a telescoping manner. The leaflet frame 1130 defines a pluralityof leaflet windows 137, wherein film defines a leaflet extending fromeach of the leaflet windows 137.

In accordance with an embodiment, the valve 100 can be configured toprevent interference with a heart conduction system by not covering abundle branch in the left ventricle when implanted, such as might beencountered with an aortic valve replacement procedure. For example, thevalve 100 can comprise a length of less than about 25 mm or less thanabout 18 mm. The valve 100 can also comprise an aspect ratio of lessthan one, wherein the ratio describes the relationship between thelength of the valve 100 to the expanded, functional diameter. However,the valve 100 can be constructed at any length and, more generally, anydesirable dimension.

In a transcatheter embodiment, in a collapsed state, the valve 100 canhave a collapsed profile that is less than about 35% of the expandedprofile. For example, the valve 100 comprising a 26 mm expanded diametercan have a collapsed diameter of less than about 8 mm, or less thanabout 6 mm. The percent difference in diameter is dependent ondimensions and materials of the valve 100 and its various applications,and therefore, the actual percent difference is not limited by thisdisclosure.

The valve 100 can further comprise a bio-active agent. Bio-active agentscan be coated onto a portion or the entirety of the film 160 forcontrolled release of the agents once the valve 100 is implanted. Thebio-active agents can include, but are not limited to, vasodilator,anti-coagulants, anti-platelet, anti-thrombogenic agents such as, butnot limited to, heparin. Other bio-active agents can also include, butare not limited to agents such as, for example,anti-proliferative/antimitotic agents including natural products such asvinca alkaloids (i.e. vinblastine, vincristine, and vinorelbine),paclitaxel, epidipodophyllotoxins (i.e. etoposide, teniposide),antibiotics (dactinomycin (actinomycin D) daunorubicin, doxorubicin andidarubicin), anthracyclines, mitoxantrone, bleomycins, plicamycin(mithramycin) and mitomycin, enzymes (L-asparaginase which systemicallymetabolizes L-asparagine and deprives cells which do not have thecapacity to synthesize their own asparagine); antiplatelet agents suchas G(GP) IIb/IIIa inhibitors and vitronectin receptor antagonists;anti-proliferative/antimitotic alkylating agents such as nitrogenmustards (mechlorethamine, cyclophosphamide and analogs, melphalan,chlorambucil), ethylenimines and methylmelamines (hexamethylmelamine andthiotepa), alkyl sulfonates-busulfan, nitrosoureas (carmustine (BCNU)and analogs, streptozocin), trazenes-dacarbazinine (DTIC);anti-proliferative/antimitotic antimetabolites such as folic acidanalogs (methotrexate), pyrimidine analogs (fluorouracil, floxuridine,and cytarabine), purine analogs and related inhibitors (mercaptopurine,thioguanine, pentostatin and 2-chlorodeoxyadenosine {cladribine});platinum coordination complexes (cisplatin, carboplatin), procarbazine,hydroxyurea, mitotane, aminoglutethimide; hormones (i.e. estrogen);anti-coagulants (heparin, synthetic heparin salts and other inhibitorsof thrombin); fibrinolytic agents (such as tissue plasminogen activator,streptokinase and urokinase), aspirin, dipyridamole, ticlopidine,clopidogrel, abciximab; antimigratory; antisecretory (breveldin);anti-inflammatory: such as adrenocortical steroids (cortisol, cortisone,fludrocortisone, prednisone, prednisolone, 6α-methylprednisolone,triamcinolone, betamethasone, and dexamethasone), non-steroidal agents(salicylic acid derivatives i.e. aspirin; para-aminophenol derivativesi.e. acetominophen; indole and indene acetic acids (indomethacin,sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac,and ketorolac), arylpropionic acids (ibuprofen and derivatives),anthranilic acids (mefenamic acid, and meclofenamic acid), enolic acids(piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone),nabumetone, gold compounds (auranofin, aurothioglucose, gold sodiumthiomalate); immunosuppressives: (cyclosporine, tacrolimus (FK-506),sirolimus (rapamycin), azathioprine, mycophenolate mofetil); angiogenicagents: vascular endothelial growth factor (VEGF), fibroblast growthfactor (FGF); angiotensin receptor blockers; nitric oxide donors;anti-sense oligionucleotides and combinations thereof; cell cycleinhibitors, mTOR inhibitors, and growth factor receptor signaltransduction kinase inhibitors; retenoids; cyclin/CDK inhibitors; HMGco-enzyme reductase inhibitors (statins); and protease inhibitors.

Transcatheter Delivery System

In an embodiment, with reference to FIG. 4A, a valve delivery system 500comprises a valve 100 having a collapsed configuration and an expandedconfiguration as previously described and an elongated flexible catheter480, such as a balloon catheter, configured to deploy the valve 100 viaendovascular access. The catheter 480 can comprise a balloon to expandthe valve 100 and/or if required, to touch up the valve 100 to ensureproper seating. The valve 100 can be mounted to the distal section ofthe catheter 480 for delivery through the vasculature. In order to holdthe valve in a collapsed configuration on the catheter 480, the valvedelivery system may further comprise a removable sheath (not shown) toclosely fit over the transcatheter valve 100.

A method of delivery can comprise the steps of radially compressing avalve into its collapsed configuration onto the distal end of anelongate flexible catheter having proximal and distal ends; deliveringthe valve to a tissue orifice, such as a native aortic valve orifice,via a transfemoral or transapical route, and expanding the valve intothe tissue orifice. The valve can be expanded by inflating a balloon.

A method of delivery can comprise the steps of radially compressing avalve into its collapsed configuration, onto the distal section of anelongated flexible catheter having proximal and distal ends. Arestraint, which can be connected to a tether that passes through theorifice of valve and the lumen of the catheter, is fitted around theposts of the valve. The valve is then delivered to a native valveorifice, such as a native aortic valve orifice, via a route of deliveryand expanded into the native orifice. The route of delivery can comprisea transfemoral or transapical route. The valve can be expanded byinflating a balloon.

Surgical Embodiments

It is appreciated that the embodiments of the valve 100 may besurgically implanted rather than using transcatheter techniques.Embodiments of a surgically implanted valve 100 may be substantially thesame as those described above, with the addition of a sewing cuff 171adjacent to the outer frame outer surface 126 a, shown in FIG. 4B, inaccordance with an embodiment. The sewing cuff 171, which is well knownin the art, is operable to provide structure that receives suture forcoupling the valve 100 to an implant site, such as the tissue orifice.The sewing cuff 171 may comprise any suitable material, such as, but notlimited to, double velour polyester. The sewing cuff 171 may be locatedcircumferentially around the outer frame 120 or perivalvular dependingfrom the outer frame 120.

Single Frame Valves

It is appreciated that embodiments of prosthetic valves are anticipatedcomprising the leaflet frame 130 and the film 160, without the outerframe 120. Referring to FIGS. 8D-8F, 11A-11B, embodiments of prostheticvalves comprising the leaflet frames 130 f-130 h are anticipated. Theconstructs of a single frame prosthetic valve in accordance withembodiments herein are provided suitable for a particular purpose. Inaccordance with embodiments of a surgically implanted valve having onlythe leaflet frame and film, may be substantially the same as thosedescribed above but without the outer frame, with the addition of asewing cuff 171 shown in FIG. 4B, in accordance with an embodiment.

Method of Making

Embodiments described herein also pertain to a method of making thevalve 100 embodiments as described herein. In order to make the variousembodiments, a cylindrical mandrel 710 can be used. With reference toFIG. 9A, the mandrel 710 comprises a structural form operable to receivethe leaflet frame 130 and outer frame 120 thereon.

With reference to FIGS. 9A-9B, an embodiment of a method of making avalve 100 comprises the steps of wrapping a first layer of film 160,e.g., a composite as described herein, into a tubular form about themandrel 710; placing the leaflet frame 130 and outer frame 120 over thefirst layer of film 160, as shown in FIG. 9A; forming a second layer offilm 160 over the leaflet frame 130 and the outer frame 120; thermallysetting the assembly; cutting the film 160 across the leaflet window topwithin the leaflet window 137, masking with release material 170 aportion of the film 160 in the leaflet window that defines the leaflet140 to prevent further bonding of leaflet 140 during subsequentprocessing steps; wrapping a second layer of film 160 into a tubularform over the leaflet frame 130, the outer frame 120, and over the firstlayer of film 160; thermal setting the assembly; remove the assemblyfrom the mandrel, telescopically insert the leaflet frame into the outerframe; placing the assembly back on the mandrel; thermal setting theassembly to couple the leaflet frame 130 to the outer frame 120 innesting engagement.

Embodiments described herein also pertain to a method of making thevalve 100 embodiments as described herein. In order to make the variousembodiments, a cylindrical mandrel 710 can be used. With reference toFIG. 12 , the mandrel 710 comprises a structural form operable toreceive the leaflet frame 130 thereon. An embodiment of a method ofmaking a valve 100 comprises the steps of wrapping a first layer of film160, e.g., a composite as described herein, into a tubular form aboutthe mandrel 710; placing the leaflet frame 130 over the first layer offilm 160, as shown in FIG. 12 ; forming a second layer of film 160 overthe leaflet frame 130; thermally setting the assembly; receiving theassembly over a cutting mandrel 712 as shown in FIGS. 13A and 13B;cutting the film 160 across the leaflet window top within the leafletwindow 137, resulting in the valve 100 of FIG. 11B.

EXAMPLES Example 1

A heart valve was produced having polymeric leaflets formed from acomposite material having an expanded fluoropolymer membrane and anelastomeric material and joined between two collapsible metallic frames.

The leaflet frame and outer frame were laser machined from a length ofSS316LVM tube hard tempered with an outside diameter of 23.0 mm and awall thickness of 0.65 mm in the shape shown illustratively andgenerally indicated in FIG. 9A. The leaflet frame 130 and outer frame120 were electro-polished resulting in 0.0127 mm material removal fromeach surface and leaving the edges rounded.

Fluorinated ethylene propylene (FEP) powder (Daikin America, OrangeburgN.Y.) was then applied to the leaflet frame 130 and outer frame 120.More specifically, the FEP powder was stirred to form an airborne“cloud” in an enclosed blending apparatus, such as a standard kitchentype blender, while the frames were suspended in the cloud. The frameswere exposed to the FEP powder cloud until a uniform layer of powder wasadhered to the entire surface of the frames. The frames were thensubjected to a thermal treatment by placing it in a forced air oven setto 320° C. for approximately three minutes. This caused the powder tomelt and adhere as a thin coating over the entire frame. The frames wereremoved from the oven and left to cool to room temperature.

Initial Assembly and Thermal Process Cycle

A 21 mm diameter vented metal cylindrical mandrel having a diametercorresponding to the inner diameter of the leaflet frame 130 and outerframe 120 was helically wrapped with sintered ePTFE fiber. A thin filmof type 1 (ASTM D3368) FEP was constructed using melt extrusion andstretching. The type 1 (ASTM D3368) FEP film was about 40 μm thick andwas about 7.7 cm wide. The mandrel was helically wrapped with one layerof this type 1 FEP film over the sintered ePTFE fiber only in the regionof outer frame.

The mandrel was radially wrapped with five layers of an ePTFE membranewith an FEP coating towards the mandrel. The ePTFE membrane wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The ePTFE membrane had a mass per area of 2.3 g/m², abubble point of 101.5 MPa, a thickness of about 356 nm, a matrix tensilestrength of 319 MPa in the longitudinal direction and 407 MPa in thetransverse direction.

The mandrel was helically wrapped with one layer of type 1 FEP film.

The diameter of the leaflet frame and outer frame were expanded slightlyand received on the wrapped mandrel with approximately a 10 mm spacebetween them, rotational alignment was not necessary.

The leaflet frame, outer frame and the space therebetween were helicallywrapped with 1 layer of type 1 FEP film.

The leaflet frame, outer frame and the space therebetween that willbecome the bridge portion 162, were circumferentially wrapped with 5layers of the same ePTFE membrane with an FEP coating as described abovewith the coating toward the mandrel.

The wrapped leaflet frame, outer frame and the space therebetween werewrapped with several layers of an ePTFE membrane imbibed with apolyimide material referred to as a release liner.

A substantially nonporous ePTFE membrane was configured into a cylinderand placed over the assembly, referred to as sacrificial tube. SinteredePTFE fiber was used to seal both ends of the sacrificial tube againstthe mandrel.

The assembly, including the mandrel, was heated in an oven capable ofapplying pneumatic pressure external to the sacrificial tube describedabove and while maintaining a vacuum internal to the mandrel for 40 minsuch that the mandrel temperature reached approximately 360° C. Theassembly was removed from the oven and allowed to cool to roomtemperature while still pressurized and under vacuum.

The sacrificial tube and release liner was removed. The sintered ePTFEfiber was removed to release the frame assembly from the mandrel.

The polymeric material was trimmed and removed from the leaflet windowsof the leaflet frame. The ends of each frame were circumferentiallytrimmed by a scalpel.

Intermediate Assembly and Thermal Process Cycle

An unsintered 15 mm diameter ePTFE tube was disposed on a 21.5 mm ventedmetal mandrel. Two layers of a substantially nonporous ePTFE membranewith a FEP coating was circumferentially wrapped on the mandrel with thecoating side towards the mandrel. The wrapped mandrel was placed in aconvection oven set to 320° C. and heated for 20 min. The ePTFE andsubstantially nonporous ePTFE membrane combined to serve as a releaseliner and was perforated to communicate pressure between the vent holesin the mandrel.

The leaflet frame was disposed onto the vented metal mandrel and ventholes were made in the apertures of the leaflet frame over the mandrelvent holes.

A leaflet material was then prepared. A membrane of ePTFE wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The ePTFE membrane had a mass per area of 0.452 g/m², athickness of about 508 nm, a matrix tensile strength of 705 MPa in thelongitudinal direction and 385 MPa in the transverse direction. Thismembrane was imbibed with a fluoroelastomer. The copolymer consistsessentially of between about 65 and 70 weight percent perfluoromethylvinyl ether and complementally about 35 and 30 weight percenttetrafluoroethylene.

The fluoroelastomer was dissolved in Novec HFE7500 (3M, St Paul, MN) ina 2.5% concentration. The solution was coated using a Mayer bar onto theePTFE membrane (while being supported by a polypropylene release film)and dried in a convection oven set to 145° C. for 30 seconds. After 2coating steps, the final ePTFE/fluoroelastomer or composite had a massper area of 1.75 g/m², 29.3% fluoropolymer by weight, a dome burststrength of about 8.6 KPa, and thickness of 0.81 μm.

The following test methods were used to characterize the ePTFE layersand the multi-layered composite. The thickness was measured with aMutitoyo Snap Gage Absolute, 12.7 mm (0.50″) diameter foot, ModelID-C112E, Serial #10299, made in Japan. The density was determined by aweight/volume calculation using an Analytical Balance Mettler PM400 NewJersey, USA. The force to break and tensile strengths were measuredusing an Instron Model #5500R Norwood, MA, load cell 50 kg, gagelength=25.4 cm, crosshead speed=25 mm/minute (strain rate=100% perminute) with flat faced jaws. Unless otherwise noted, these test methodswere used to generate the data in subsequent examples.

Ten layers of the composite leaflet material was wrapped around theleaflet frame with an elastomer rich side of the composite facingtowards the mandrel. In exemplary embodiments, the composite material isoriented to have a predetermined matrix tensile strength along adirection generally perpendicular with the longitudinal axis of thecombined tool assembly. More specifically, the predetermined matrixtensile strength is about 705 MPa.

The mandrel was radially wrapped with one layer of a substantiallynonporous ePTFE membrane with an FEP coating towards the mandrel with aspacing 8 mm from the base of the leaflet frame. The ePTFE membrane wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The ePTFE membrane had a mass per area of about 11 g/m²,a thickness of about 5.5 μm, a matrix tensile strength of 310 MPa in thelongitudinal direction and 103 MPa in the transverse direction.

A Kapton® (EI DuPont de Nemours, Inc., Wilmington, DE) polyimide filmacting as a mask was wrapped over the substantially nonporous ePTFEmembrane with an FEP coating layer.

The outer frame was placed on the mandrel with 10 mm spacing between theleaflet frame and the outer frame. The leaflet frame and the outer framewere aligned such that the longitudinal outer frame posts were collinearwith the leaflet frame posts.

The leaflet frame and outer frame were wrapped with 24 layers of thecomposite leaflet material described earlier with an elastomer rich sideof the composite facing towards the mandrel. In exemplary embodiments,the composite material is oriented to have a predetermined matrixtensile strength along a direction generally perpendicular with thelongitudinal axis of the combined tool assembly. More specifically, thepredetermined matrix tensile strength is about 705 MPa.

The final leaflet was comprised of 29.3% fluoropolymer by weight with athickness of approximately 27 μm. Each leaflet had 34 layers of thecomposite and a ratio of thickness/number of layers of 0.8 μm.

The mandrel was again radially wrapped with one layer of a substantiallynonporous ePTFE membrane with an FEP coating towards the mandrel with aspacing 8 mm from the base of the leaflet frame.

The assembly was wrapped with several layers of the sacrificial releaseliner. A sacrificial tube was placed over the assembly and sinteredePTFE fiber was used to seal both ends of the sacrificial tube againstthe mandrel.

The assembly was processed in an oven capable of applying pneumaticpressure external to the sacrificial material configured into a tubedescribed above and while maintaining a vacuum internal to the tube for25 min such that the mandrel temperature reached approximately 330° C.The assembly was removed from the oven and allowed to cool to roomtemperature while still pressurized and under vacuum.

The sacrificial tube and liner were removed from the frame assembly andthe frame assembly was removed from the mandrel. The Kapton® mask wasremoved.

A scalpel was used to circumferentially trim the free edge of eachleaflet and the distal end of leaflet frame.

Final Assembly and Thermal Process Cycle

The outer frame was radially expanded to a 24 mm diameter using atapered mandrel.

A release liner as described above was placed on a 21.5 mm ventedmandrel.

Three Kapton® masks were cut to the shape of leaflet window with a 30 mmtapered extension.

The frames with leaflet material were placed onto the mandrel and thetapered extensions of the Kapton® masks were inserted under the top ringof the leaflet frame from the trimmed end and were advanced axiallyuntil the masks aligned with the leaflet window.

The leaflet frame was wrapped with 2 layers of the type 1 FEP film.

A hot iron was used to remove the FEP film from the leaflet windowregion by melting it away from the perimeter and to tack the FEP film inall regions of leaflet frame outside the masks.

Vent holes were made within all the frame apertures and in the polymertube region connecting the inner and outer frame.

While holding the leaflet frame in place, the outer frame was coaxiallydisposed over the leaflet frame by telescopically inverting the bridgeportion of the contiguous tube.

The entire frame assembly was circumferentially wrapped with onesubstantially nonporous ePTFE membrane with an FEP coating towards themandrel.

The assembly was wrapped with several layers of the sacrificial releaseliner. A sacrificial tube was placed over the assembly and sinteredePTFE fiber was used to seal both ends of the sacrificial tube againstthe mandrel.

The assembly was processed in an oven capable of applying pneumaticpressure external to the sacrificial material configured into a tubedescribed above and while maintaining a vacuum internal to the tube for25 min such that the mandrel temperature reached approximately 330° C.The assembly was removed from the oven and allowed to cool to roomtemperature while still pressurized and under vacuum.

The frame assembly was removed from the mandrel.

A scalpel was used to circumferentially trim each end of leaflet frame.

The Kapton was rotationally peeled away from inside the outer frame andaway from leaflets.

Using scissors, both ends of the leaflet frame were trimmed to followframe contour.

The resulting valve 100 includes leaflets 140 formed from a compositematerial with more than one fluoropolymer layer having a plurality ofpores and an elastomer present in substantially all of the pores of themore than one fluoropolymer layer. Each leaflet 140 is movable between aclosed position, shown in FIG. 3B, in which blood is substantiallyprevented from flowing through the valve assembly, and an open position,shown in FIG. 3A, in which blood is allowed to flow through the valveassembly. Thus, the leaflets 140 of the valve 100 cycle between theclosed and open positions generally to regulate blood flow direction ina human patient.

The performance of the valve leaflets was characterized on a real-timepulse duplicator that measured typical anatomical pressures and flowsacross the valve. The flow performance was characterized by thefollowing process:

The valve assembly was potted into a silicone annular ring (supportstructure) to allow the valve assembly to be subsequently evaluated in areal-time pulse duplicator. The potting process was performed accordingto the recommendations of the pulse duplicator manufacturer (ViVitroLaboratories Inc., Victoria BC, Canada)

The potted valve assembly was then placed into a real-time left heartflow pulse duplicator system. The flow pulse duplicator system includedthe following components supplied by VSI Vivitro Systems Inc., VictoriaBC, Canada: a Super Pump, Servo Power Amplifier Part Number SPA 3891; aSuper Pump Head, Part Number SPH 5891B, 38.320 cm² cylinder area; avalve station/fixture; a Wave Form Generator, TriPack Part Number TP2001; a Sensor Interface, Part Number VB 2004; a Sensor AmplifierComponent, Part Number AM 9991; and a Square Wave Electro Magnetic FlowMeter, Carolina Medical Electronics Inc., East Bend, NC, USA.

In general, the flow pulse duplicator system uses a fixed displacement,piston pump to produce a desired fluid flow through the valve undertest.

The heart flow pulse duplicator system was adjusted to produce thedesired flow (5 L/min), mean pressure (15 mmHg), and simulated pulserate (70 bpm). The valve under test was then cycled for about 5 to 20minutes.

Pressure and flow data were measured and collected during the testperiod, including right ventricular pressures, pulmonary pressures, flowrates, and pump piston position. Shown illustratively in Figure XX is agraph of typical data outputs from the heart flow pulse duplicatorsystem.

Parameters used to characterize the valve are effective orifice area andregurgitant fraction. The effective orifice area (EOA), which can becalculated as follows: EOA(cm²)=Q_(rms)/(51.6*(ΔP)^(1/2)) where Q_(rms)is the root mean square systolic/diastolic flow rate (cm³/s) and ΔP isthe mean systolic/diastolic pressure drop (mmHg).

Another measure of the hydrodynamic performance of a valve is theregurgitant fraction, which is the amount of fluid or blood regurgitatedthrough the valve divided by the stroke volume.

The hydrodynamic performance measured values were; EOA=2.06 cm², andregurgitant fraction=8.2%.

Example 2

Another valve was made as described in Example 1 with the followingexceptions.

Initial Assembly and Thermal Process Cycle

The diameter of the leaflet frame and outer frame were expanded slightlyand received on the wrapped mandrel with 16 mm space between them,rotational alignment if the leaflet frame and outer frame was made.

Final Assembly and Thermal Process Cycle

A scalpel was used to cut above the mechanical linking tab. The tab wasdeformed to link inner and outer frames.

The resulting valve 100 includes leaflets 140 formed from a compositematerial with more than one fluoropolymer layer having a plurality ofpores and an elastomer present in substantially all of the pores of themore than one fluoropolymer layer. Each leaflet 140 is movable between aclosed position, shown in FIG. 3B, in which blood is substantiallyprevented from flowing through the valve assembly, and an open position,shown in FIG. 3A, in which blood is allowed to flow through the valveassembly. Thus, the leaflets 140 of the valve 100 cycle between theclosed and open positions generally to regulate blood flow direction ina human patient.

The hydrodynamic performance was measured. The performance values were;EOA=2.3 cm² and regurgitant fraction=11.8%.

Numerous characteristics and advantages have been set forth in thepreceding description, including various alternatives together withdetails of the structure and function of the devices and/or methods. Thedisclosure is intended as illustrative only and as such is not intendedto be exhaustive. It will be evident to those skilled in the art thatvarious modifications can be made, especially in matters of structure,materials, elements, components, shape, size and arrangement of partsincluding combinations within the principles of the disclosure, to thefull extent indicated by the broad, general meaning of the terms inwhich the appended claims are expressed. To the extent that thesevarious modifications do not depart from the spirit and scope of theappended claims, they are intended to be encompassed therein.

Example 3 (Single Frame Valve)

In exemplary embodiments, a heart valve having polymeric leaflets formedfrom a composite material having an expanded fluoropolymer membrane andan elastomeric material and joined to a semi-rigid, non-collapsiblemetallic frame, and further a having strain relief was constructedaccording to the following process:

A leaflet frame was laser machined from a length of MP35N cobaltchromium tube hard tempered with an outside diameter of 26.0 mm and awall thickness of 0.6 mm in the shape. The frame was electro-polishedresulting in 0.0127 mm material removal from each surface and leavingthe edges rounded. The frame was exposed to a surface roughening step toimprove adherence of leaflets to the frame. The frame was cleaned bysubmersion in an ultrasonic bath of acetone for approximately fiveminutes. The entire metal frame surface was then subjected to a plasmatreatment using equipment (e.g. PVA TePLa America, Inc Plasma Pen,Corona, CA) and methods commonly known to those having ordinary skill inthe art. This treatment also served to improve the wetting of thefluorinated ethylene propylene (FEP) adhesive.

FEP powder (Daikin America, Orangeburg N.Y.) was then applied to theframe. More specifically, the FEP powder was stirred to form an airborne“cloud” in an enclosed blending apparatus, such as a standard kitchentype blender, while the frame is suspended in the cloud. The frame wasexposed to the FEP powder cloud until a layer of powder was adhered tothe entire surface of the frame. The frame was then subjected to athermal treatment by placing it in a forced air oven set to 320° C. forapproximately three minutes. This caused the powder to melt and adhereas a thin coating over the entire frame. The frame was removed from theoven and left to cool to approximately room temperature.

The strain relief was attached to the frame in the following manner. Athin (122 μm) walled sintered 15 mm diameter ePTFE tube was disposed ona 24.5 mm vented metal mandrel by stretching radially over a taperedmandrel. Two layers of a substantially nonporous ePTFE membrane with acontinuous FEP coating was circumferentially wrapped on the mandrel withthe FEP side towards the mandrel. The wrapped mandrel was placed in aconvection oven set to 320° C. and heated for 20 min. The ePTFE andsubstantially nonporous ePTFE membrane combined to serve as an innerrelease liner and was perforated using a scalpel blade to communicatepressure between the vent holes in the mandrel. This entire releaseliner is removed in a later step.

A 5 cm length of the thick (990μ) walled partially sintered 22 mm innerdiameter ePTFE tube (density=0.3 g/cm³) was disposed onto the 24.5 mmvented metal mandrel with release liner. The ePTFE tube inner diameterwas enlarged by stretching it on a tapered mandrel to accommodate thelarger mandrel diameter.

A thin (4 μm) film of type 1 FEP (ASTM D3368) was constructed using meltextrusion and stretching. One layer of the FEP was wrapped over the 5 cmlength of the ePTFE tube.

The FEP powder coated frame was disposed onto the vented metal mandrelgenerally in the middle of the 5 cm span of ePTFE tube and FEP film.

One layer of the FEP was wrapped over the frame and 5 cm length of theePTFE tube.

A second 5 cm length of the 990 μm thick/22 mm inner diameter ePTFE tubewas disposed onto the assembly layered onto 24.5 mm vented metal mandrelby stretching its radius over a tapered mandrel to accommodate thelarger construct diameter.

A substantially nonporous ePTFE membrane was configured into a cylinderat a diameter larger than the construct and placed over the assembly,referred to as sacrificial tube. Sintered ePTFE fiber (e.g. Gore Rastex®Sewing Thread, Part # S024T2, Newark Del.) was used to seal both ends ofthe sacrificial tube against the mandrel.

The assembly, including the mandrel, was heated in a convection oven(temperature set point of 390° C.) capable of applying pneumaticpressure of 100 psi external to the sacrificial tube described abovewhile maintaining a vacuum internal to the mandrel. The assembly wascooked for 40 min such that the mandrel temperature reachedapproximately 360° C. (as measured by a thermocouple direct contact withthe inner diameter of the mandrel). The assembly was removed from theoven and allowed to cool to approximately room temperature while stillunder 100 psi pressure and vacuum.

The sacrificial tube was then removed. Approximately 30 psi of pressurewas applied to the internal diameter of the mandrel to assist in removalof the assembly. The inner release liner was peeled away from theinternal diameter of the assembly by inverting the liner and axiallypulling it apart.

The polymeric material was trimmed with a scalpel and removed from theleaflet windows and bottom of the frame leaving approximately 0.5 to 1.0mm of material overhang.

A leaflet material was then prepared. A membrane of ePTFE wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The ePTFE membrane had a mass per area of 0.452 g/m², athickness of about 508 nm, a matrix tensile strength of 705 MPa in thelongitudinal direction and 385 MPa in the transverse direction. Thismembrane was imbibed with a fluoroelastomer. The copolymer consistsessentially of between about 65 and 70 weight percent perfluoromethylvinyl ether and complementally about 35 and 30 weight percenttetrafluoroethylene.

The fluoroelastomer was dissolved in Novec HFE7500 (3M, St Paul, MN) ina 2.5% concentration. The solution was coated using a mayer bar onto theePTFE membrane (while being supported by a polypropylene release film)and dried in a convection oven set to 145° C. for 30 seconds. After 2coating steps, the final ePTFE/fluoroelastomer or composite had a massper area of 1.75 g/m², 29.3% fluoropolymer by weight, a dome burststrength of about 8.6 KPa, and thickness of 0.81 μm.

The final leaflet was comprised of 28.22% fluoropolymer by weight with athickness of 50.3 μm. Each leaflet had 26 layers of the composite and aratio of thickness/number of layers of 1.93 μm.

The resulting valve assembly includes leaflets formed from a compositematerial with more than one fluoropolymer layer having a plurality ofpores and an elastomer present in substantially all of the pores of themore than one fluoropolymer layer. Each leaflet is movable between aclosed position, shown illustratively in FIG. 3B, in which blood issubstantially prevented from flowing through the valve assembly, and anopen position, shown illustratively in FIG. 3A, in which blood isallowed to flow through the valve assembly. Thus, the leaflets of thevalve assembly cycle between the closed and open positions generally toregulate blood flow direction in a human patient.

The hydrodynamic performance was measured prior to accelerated weartesting. The performance values were; EOA=2.4 cm² and regurgitantfraction=11.94%.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the present embodimentswithout departing from the spirit or scope of the embodiments. Thus, itis intended that the present embodiments cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

What is claimed:
 1. A prosthetic valve comprising: a support structurehaving a longitudinal axis and defining a leaflet attachment zonebetween a pair of adjacent commissure posts, the pair of adjacentcommissure posts defining a chord length; and a leaflet coupled to andextending from the leaflet attachment zone, the leaflet having leafletsides, a leaflet base, and a leaflet free edge opposite the leafletbase, the leaflet base and the leaflet sides being coupled to thesupport structure, the leaflet including a base segment defining astraight line that is shorter than the chord length and is adjacent tothe leaflet base, the leaflet operable to bend about the base segmentduring opening-closing cycles associated with blood pressuredifferentials across the prosthetic valve, the prosthetic valve beingoperable to be reduced in diameter for transcatheter delivery andradially expanded for deployment.
 2. The prosthetic valve of claim 1,wherein the leaflet is defined by a material coupled to an outer surfaceof the support structure.
 3. The prosthetic valve of claim 1, whereinthe leaflet is defined by a material coupled to an inner surface of thesupport structure.
 4. The prosthetic valve of claim 1, wherein theleaflet is defined by a material coupled to an inner surface and anouter surface of the support structure.
 5. The prosthetic valve of claim1, wherein the leaflet includes a first film positioned inside thesupport structure and a second film positioned outside the supportstructure, the first film bonded to the second film.
 6. The prostheticvalve of claim 1, wherein the leaflet is characterized by an absence ofintersecting creases.
 7. The prosthetic valve of claim 1, wherein thesupport structure comprises a plurality of frame elements spanning theleaflet attachment zone.
 8. The prosthetic valve of claim 7, wherein theplurality of frame elements are associated with an outer framepositioned coaxially with the support structure.
 9. The prosthetic valveof claim 1, wherein the leaflet is operable to bend along and about thebase segment.
 10. The prosthetic valve of claim 1, wherein the basesegment is spaced from the leaflet attachment zone.
 11. A prostheticvalve comprising: a support structure having a longitudinal axis anddefining a leaflet attachment zone between a pair of adjacent commissureposts; and a leaflet coupled to and extending from the leafletattachment zone, the leaflet having leaflet sides, a leaflet base, and aleaflet free edge opposite the leaflet base, the leaflet base and theleaflet sides being coupled to the support structure, the leafletincluding a straight base segment adjacent to the leaflet base, theleaflet including a planar zone having a planar zone base coincidentwith the straight base segment, the leaflet operable to bend about thestraight base segment during opening-closing cycles associated withblood pressure differentials across the prosthetic valve, the prostheticvalve being operable to be reduced in diameter for transcatheterdelivery and radially expanded for deployment.
 12. The prosthetic valveof claim 11, wherein the pair of adjacent commissure posts defining achord length, and wherein the straight base segment is shorter than thechord length.
 13. The prosthetic valve of claim 11, wherein the straightbase segment defines a virtual leaflet base about which a portion of theleaflet is operable to bend during opening and closing of the leaflet.14. The prosthetic valve of claim 11, wherein the leaflet is defined bya material coupled to an inner surface and an outer surface of thesupport structure.
 15. The prosthetic valve of claim 11, wherein theleaflet includes a first film positioned inside the support structureand a second film positioned outside the support structure, the firstfilm bonded to the second film.
 16. A prosthetic valve comprising: asupport structure having a longitudinal axis and defining a leafletattachment zone between a pair of adjacent commissure posts; and aleaflet coupled to and extending from the leaflet attachment zone, theleaflet having leaflet sides, a leaflet base, and a leaflet free edgeopposite the leaflet base, the leaflet base and the leaflet sides beingcoupled to the support structure, the leaflet including a flat portiondefining a shelf portion, the leaflet operable to bend from the flatportion along a straight base segment towards the free edge duringopening-closing cycles associated with blood pressure differentialsacross the prosthetic valve, the prosthetic valve being operable to bereduced in diameter for transcatheter delivery and radially expanded fordeployment.
 17. The prosthetic valve of claim 16, wherein the leaflet isdefined by a material coupled to an inner surface of the supportstructure.
 18. The prosthetic valve of claim 16, wherein the supportstructure comprises a plurality of frame elements spanning the leafletattachment zone.
 19. The prosthetic valve of claim 18, wherein theplurality of frame elements are associated with an outer framepositioned coaxially with the support structure.